(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → HCID 86689781, compound

HRID 1396437Notes

Reaction equation

HRID 1396437 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([CH2:20][CH2:21][CH3:22])[N:13]=2)[CH:3]=1.[NH2:23][C@@H:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]1[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34]>CN1C(=O)CCC1.C(OCC)(=O)C>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:23][C@@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]2[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([CH2:20][CH2:21][CH3:22])[N:13]=1)(=[O:9])[NH2:10]

Participants

5

Reactant 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected3×HCID 86689780HCID 86689780, compound

Product 1

HCID 86689781HCID 86689781, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 6-chloro-4-(5-methoxy-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (200 mg, 622 μmol) in NMP (2.07 mL) was added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (133 mg, 622 μmol) and the mixture heated at 140° C. for 20 h. A second portion of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (133 mg, 622 μmol) was added and the mixture stirred for a further 7 h. A final portion of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (133 mg, 622 μmol) was added and the mixture heated for 16 h, then cooled, diluted with ethyl acetate, and washed with brine (4×). The organic layer was collected, concentrated in vacuo, and the residue obtained was purified by chromatography (silica, 1 to 5% methanol in dichloromethane) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-methoxy-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (96 mg, 192 μmol, 31%) as a light brown solid. MS (EI/CI) m/z: 500.2 [M+H].

Workup

  1. temperaturethe mixture heated for 16 h
  2. temperaturecooled
  3. washwashed with brine (4×)
  4. customThe organic layer was collected
  5. concentrationconcentrated in vacuo
  6. customthe residue obtained
  7. customwas purified by chromatography (silica, 1 to 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-dcd53cb81814478eae791446a921d294
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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